The present invention relates to single and multiple layer collagen films that are useful for improved sustained release delivery of pharmaceuticals.
Various membranes containing collagen have been used in the prior art. Abbenhaus et al., Surg. Forum 16:477-478 (1965) disclosed collagen films of 2 to 3 millimeter thickness that were produced by heating and dehydrating collagen extracted from cow hides. Chu disclosed non-chemically crosslinked collagen implants produced by compression, which are useful for sustained drug delivery [European Patent Application 187014, published Jul. 9, 1986; U.S. Pat. No. 4,600,533, issued Jul. 15, 1986; U.S. Pat. No. 4,655,980, issued Apr. 7, 1987; U.S. Pat. No. 4,689,399, issued Aug. 25, 1987; and PCT Patent Application WO 90/00060, published Jun. 28, 1989]. Cioca [U.S. Pat. No. 4,412,947, issued Nov. 1, 1983], disclosed an essentially pure collagen sheet made by freeze drying a suspension of collagen in an organic acid. Kuroyanagai et al. [European Patent Application 167828, published Jan. 15, 1984; U.S. Pat. No. 4,642,118, issued Feb. 10, 1987], disclosed an artificial skin composed of two layers: collagen and a poly-alpha-amino acid. Berg et al. [U.S. Pat. No. 4,841,962, issued Jun. 27, 1989], disclosed a wound dressing composed of three layers: an adhesive, a cross-linked collagen matrix, and a multilayer polymer film. Holman, U.S. Pat. No. 4,950,699, issued Aug. 21, 1990, disclosed a wound dressing consisting of less than 10 percent collagen mixed with an acrylic adhesive. Cioca et al., British Patent 1,347,582, disclosed a collagenic wound dressing consisting of a freeze dried polydisperse collagen mixture. Steffan et al., European Patent 069260, published Jan. 12, 1983, disclosed a collagen insert consisting of high purity native collagen. Zimmerman et al. [U.S. Pat. No. 4,453,939, issued Jun. 12, 1984], disclosed a wound healing composition containing collagen coated with fibrinogen, factor XIII fibrinogen, and/or thrombin. Leibovich et al. [U.S. Pat. No. 4,808,402, issued February 1989], disclosed a composition for treating wounds comprising collagen, bioerodible polymer, and tumor necrosis factor. Yannas and Burke [J. Biomed. Mat. Res. 14:68-81 (1980)], have reviewed the design of artificial skin, some examples of which contain collagen. Chvapil et al., Int. Rev. Connect. Tissue Res. 6:1-61 (1973), particularly at pages 51 to 52; and Pachence et al., Med. Device and Diag. Ind., 9:49-55 (1987), disclose various uses of collagen, including its use as a drug delivery vehicle.
In addition, collagen has been used as a component in pharmaceutical sponges [Artandi, U.S. Pat. No. 3,157,524, issued Nov. 17, 1964; Berg et al., U.S. Pat. No. 4,320,201, issued Mar. 16, 1982; Berg et al., U.S. Pat. No. 4,837,285, issued Jun. 6, 1989; Doillon et al., Scanning Electron Microscopy III:1313-1320 (1984); Doillon and Silver, Biomaterials 7:3-8 (1986); Doillon et al., Biomaterials 8:195-200 (1987); Oluwasanmi et al., J. Trauma 16:348-353 (1976); Collins et al., Surg. Forum 27:551-553 (1976)] and salves [PCT Patent Application WO 86/03122, published Jun. 5, 1986]. Collagen has also been used for wound healing in conjunction with electrical currents [U.S. Pat. No. 4,937,323, issued Jun. 26, 1990].
Although some previously utilized collagen containing films have demonstrated sustained release characteristics, they are by no means optimal for steady, even, and continuous release of therapeutic agents over an extended period of time. The present invention provides a much desired improvement in wound dressings by providing for such a steady, even, and continuous release of therapeutic agents over an extended period of time.